Abstract

The human complement system is one of the principal effector systems of innate immunity and consists of more than 30 serum
and cell surface proteins. Most complement components show a striking modular structure, which makes evolutionary studies
feasible. The evolutionary origin of the complement system can be traced back to the common ancestor of eumetazoa, predating
by far the origin of the canonical adaptive immunity unique to the jawed vertebrates. Although the complement system has been
conserved by all deuterostomes analysed thus far, it has been lost multiple times independently in the protostome lineage.
Sophistication of the complement system from a simpler system by gene duplications and exon shuffling occurred in the vertebrate
lineage.

Key Concepts:

The complement system is one of the most ancient body defence mechanisms of eumetazoa.

Most complement components have a characteristic modular structure.

The modern complement system was established in a common ancestor of jawed vertebrates by gene duplication and exon shuffling
of the primitive complement genes.

The complement system has been lost multiple times independently in protostome lineages, whereas it has been retained by all
deuterostomes analysed so far.

The thioester‐containing protein family is subdivided into two subfamilies, the C3 and A2M subfamilies.

Modular structure of human complement components and chromosomal localisation of the encoding genes. Protein module designation
and modular structure are adapted from Volanakis and Frank . Chromosomal localisation of the complement genes is adapted from the Complement Genetics Website (http://www.complement‐genetics.uni‐mainz.de/chromtab.htm).

Figure 2.

Phylogenetic tree of TEP family. The entire amino acid sequences were aligned by ClustalX and MEGA5, and phylogenetic tree was constructed using the
neighbour‐joining method based on the poisson model. The analysis involved 41 amino acid sequences. In this tree, gaps in
the alignment were excluded. There were a total of 954 positions in the final dataset. The scale bar indicates substitutions/site.

Figure 3.

Hypothetical evolutionary history of the genes for MASP, C1r and C1s (Nonaka and Miyazawa, ).